Control of mean arterial pressure using a closed-loop system for norepinephrine infusion in severe brain injury patients: the COMAT randomized controlled trial.

Brain injury patients require precise blood pressure (BP) management to maintain cerebral perfusion pressure (CPP) and avoid intracranial hypertension. Nurses have many tasks and norepinephrine titration has been shown to be suboptimal. This can lead to limited BP control in patients that are in critical need of cerebral perfusion optimization. We have designed a closed-loop vasopressor (CLV) system capable of maintaining mean arterial pressure (MAP) in a narrow range and we aimed to assess its performance when treating severe brain injury patients. Within the first 48 h of intensive care unit (ICU) admission, 18 patients with a severe brain injury underwent either CLV or manual norepinephrine titration. In both groups, the objective was to maintain MAP in target (within ± 5 mmHg of a predefined target MAP) to achieve optimal CPP. Fluid administration was standardized in the two groups. The primary objective was the percentage of time patients were in target. Secondary outcomes included time spent over and under target. Over the four-hour study period, the mean percentage of time with MAP in target was greater in the CLV group than in the control group (95.8 ± 2.2% vs. 42.5 ± 27.0%, p < 0.001). Severe undershooting, defined as MAP < 10 mmHg of target value was lower in the CLV group (0.2 ± 0.3% vs. 7.4 ± 14.2%, p < 0.001) as was severe overshooting defined as MAP > 10 mmHg of target (0.0 ± 0.0% vs. 22.0 ± 29.0%, p < 0.001). The CLV system can maintain MAP in target better than nurses caring for severe brain injury patients.

Comparison of Pressure Reactivity Index and Mean Velocity Index to Evaluate Cerebrovascular Reactivity During Induced Arterial Blood Pressure Variations in Severe Brain Injury.

OBJECTIVES: To compare the assessment of cerebral autoregulation by cerebrovascular reactivity indices based on intracranial pressure (Pressure Reactivity Index, PRx) and on transcranial Doppler (Mean Velocity Index, Mx) during controlled variations of arterial blood pressure in severe brain injury. Primary outcome was the agreement between both cerebrovascular reactivity indices measured by the Bland-and-Altman method. Secondary outcomes were the association of cerebrovascular reactivity indices with arterial blood pressure variation, and the comparison of optimal cerebral perfusion pressures determined by both indices. METHODS: All consecutive comatose (Glasgow Coma Scale < 8) patients from the surgical intensive care unit of Bicetre Hospital who had an acute brain injury on computerized tomography and needed vasopressor support were prospectively included. Step-by-step arterial pressure variations using vasopressors were performed to compare PRx and Mx and to calculate optimal cerebral perfusion pressure (CPPopt). MEASUREMENTS AND MAIN RESULTS: 15 patients were included. Mean difference between both indices measured by Bland-and-Altman plot was - 0.07 (IC 95% [- 1.02 to 0.87]). Mx was significantly associated with arterial pressure variation (one-way ANOVA test, p = 0.007), whereas PRx was not (p = 0.44). Optimal cerebral perfusion pressure calculated with PRx and Mx was respectively 11 and 15mmHg higher than the mean perfusion pressure prescribed. Optimal cerebral perfusion pressure calculation was possible in all cases. CONCLUSIONS: Cerebral vasoreactivity indices calculated with intracranial pressure or transcranial Doppler show only moderate agreement. Both indices nonetheless suggest substantially higher optimal cerebral perfusion pressure than those currently provided by international guidelines.

Reactivation of Epstein-Barr virus among intensive care patients: a prospective observational study.

PURPOSE: Herpesvirus reactivation has been documented among patients in the intensive care unit (ICU) and is associated with increased morbidity and mortality, particularly for cytomegalovirus (CMV). Epstein-Barr virus (EBV) has been poorly studied despite >95% of the population being seropositive. Our preliminary study suggested an association between EBV reactivation and increased morbidity and mortality. This study aimed to investigate this association among patients admitted to the ICU. METHODS: In this multicenter prospective study, polymerase chain reaction was performed to quantify EBV in patients upon ICU admission and then twice a week during their stay. Follow-up was 90 days. RESULTS: The study included 129 patients; 70 (54.3%) had EBV reactivation. On day 90, there was no difference in mortality rates between patients with and without reactivation (25.7% vs 15.3%, p = 0.22). Patients with EBV reactivation at admission had increased mortality compared with those without reactivation and those with later reactivation. EBV reactivation was associated with increased morbidity. Patients with EBV reactivation had fewer ventilator-free days at day 28 than those without reactivation (18 [1-22] vs. 21 days [5-26], p = 0.037) and a higher incidence of acute respiratory distress syndrome (34.3% vs. 17%, p = 0.04), infections (92.9% vs. 78%, p = 0.03), and septic shock (58.6% vs. 32.2%, p = 0.004). More patients with EBV reactivation required renal replacement therapy (30% vs. 11.9%, p = 0.02). EBV reactivation was also associated with a more inflammatory immune profile. CONCLUSION: While EBV reactivation was not associated with increased 90-day mortality, it was associated with significantly increased morbidity.

Admission serum myoglobin and the development of acute kidney injury after major trauma.

BACKGROUND: Myoglobin and creatine kinase (CK) are both established markers of muscle injury but their hospital admission values have never been compared to predict post-traumatic acute kidney injury (AKI). METHODS: An observational registry study of consecutive trauma patients admitted to a major regional trauma centre. The primary outcome was stage 1 or more AKI in the first 7 days after trauma. We assessed the association of hospital admission myoglobin or CK with development of AKI both alone and when added to two existing risk prediction models for post traumatic AKI. RESULTS: Of the 857 trauma patients (median age 36 [25-52], 96% blunt trauma, median ISS of 20 [12-47]) included, 102 (12%) developed AKI. Admission myoglobin performed better than CK to predict AKI any stage with an AUC-ROC of 0.74 (95% CI 0.68-0.79) and 0.63 (95% CI 0.57-0.69), respectively (p < 0.001). Admission myoglobin also performed better than CK to predict AKI stage 2 or 3 [AUC-ROC of 0.79 (95% CI 0.74-0.84) and 0.74 (95% CI 0.69-0.79), respectively (p < 0.001)] with a best cutoff value of 1217 µg/L (sensitivity 74%, specificity 77%). Admission myoglobin added predictive value to two established models of AKI prediction and showed significant ability to reclassify subjects regarding AKI status, while admission CK did not. Decision curve analysis also revealed that myoglobin added net benefit to established predictive models. Admission myoglobin was better than CK at predicting development of significant rhabdomyolysis. CONCLUSIONS: Admission myoglobin better predicts the development of AKI and severe rhabdomyolysis after major trauma. Admission myoglobin should be added in established predictive models of post-traumatic AKI to early identify high-risk patients.